Trifluridine tipiracil with bevacizumab in refractory metastatic colorectal cancer with a convenient two weekly schedule: An Indian single center experience.

Abstract

e15612 Background: Refractory metastatic colorectal cancer (CRC) is a challenging situation with most patients showing modest response to treatment with trifluridine tipiracil (FTD-TPI) or regorafenib. In the recent phase 3 Sunlight trial, FTD-TPI with bevacizumab showed better efficacy than FTD-TPI alone with median overall survival (OS) of 10.8 months versus 7.5 months, and median progression free survival (PFS) of 5.6 months versus 2.4 months respectively, making this a preferred 3 rd line option. The most common adverse events were neutropenia, nausea, and anemia and discontinuation of the trial regimen was reported in 12.6%. We evaluated this regimen in Indian patients, as there is limited data of treatment with this regimen from India. Methods: This was a retrospective observational study of refractory metastatic CRC patients treated between April 2023 to Dec 2024 at Manipal Hospital, Bangalore, India. FTD-TPI was given at 35mg/m 2 , twice daily, on days 1-5 and days 15-19 with bevacizumab at 5 mg/kg on days 1 and 15, and the cycle was repeat 4 weekly. Two weekly schedule was evaluated to reduce toxicity of low counts and to make the regimen convenient, thus, improving compliance. The endpoints were PFS, OS and safety. Results: 27 patients received treatment with FTD-TPI with bevacizumab. There were 8 females and 19 males. 18 had left sided and 9 had right sided cancer. Biomarker analysis revealed 16 KRAS mutations with 2 having K RAS G12C, 2 NRAS mutations, 2 B-RAF mutation, 1 MMR deficient and 1 Her2 3+ overexpression. 17 patients (63%) received this combination in 3 rd line and 10 (37%) received in 4 th line and beyond. All patients had progressed on fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab and anti-EGFR therapy (in RAS and B RAF wild type patients) in the prior lines. The median PFS was 6 months and median OS was 14 months. Most common side effects were fatigue, neutropenia and anemia. 15 patients (55.5%) required dose reduction of FTD-TPI due to toxicities and 3 patients (11%) discontinued treatment due to intolerance. Conclusions: The combination of FTD-TPI with bevacizumab was an effective option in our refractory metastatic CRC patients. Two weekly regimen was better tolerated and also convenient in this heavily pre-treated population. Considering the significant dose reductions due to low counts, we would suggest studying this two weekly combination regimen at a lower starting dose of FTD-TPI in a larger study in India.